The specific aims of this project are: (1) to search for the primary action and site of action of the diabetic alleles (db and db super 2J) that cause a disease in mice resembling maturity onset diabetes mellitus in man; (2) to define the physiology, biochemistry, and histopathology of the disease caused by these two alleles in different genetic backgrounds; and (3) to compare the effects of the diabetes alleles with those caused by unrelated alleles such as obese (ob) and the yellow alleles (A super y, A super vy, A super iy, and A super sy) which also cause hyperphagia, obesity, hyperinsulinemia and mild hyperglycemia.